U.S. BRAND NAMES — Miochol®-E
CANADIAN BRAND NAMES — Miochol®-E
THERAPEUTIC CATEGORY Cholinergic Agent, OphthalmicOphthalmic Agent, Miotic
DOSING — Ophthalmic: Adults: Instill 0.5-2 mL of 1% injection (5-20 mg)
(For additional information see "Acetylcholine: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder for solution, intraocular, as chloride: Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
GENERIC AVAILABLE — No
ADMINISTRATION — Ophthalmic: Instill into anterior chamber before or after securing one or more sutures; instillation should be gentle and parallel to the iris face and tangential to the pupil border; in cataract surgery, acetylcholine should be used only after delivery of the lens
USE — Produces complete miosis in cataract surgery, keratoplasty, iridectomy and other anterior segment surgery where rapid miosis is required
ADVERSE REACTIONS Cardiovascular: Transient bradycardia and hypotension
Central nervous system: Headache
Ocular: Iris atrophy, temporary lens opacities (attributed to osmotic effect of 5% mannitol present in preparation)
Respiratory: Dyspnea
Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to acetylcholine chloride or any component; acute iritis and acute inflammatory disease of the anterior chamber
PRECAUTIONS — Systemic effects rarely occur, but can cause problems for patients with acute CHF, bronchial asthma, peptic ulcer, hyperthyroidism, GI spasm, and urinary tract obstruction
WARNINGS — Open under aseptic conditions only
DRUG INTERACTIONS — Flurbiprofen decreases effectiveness; sodium nitrate antagonizes acetylcholine's effects
PREGNANCY RISK FACTOR — C (show table)
STABILITY — Prepare solution immediately before use; do not use solution which is not clear and colorless
MECHANISM OF ACTION — Causes contraction of the sphincter muscles of the iris, resulting in miosis and contraction of the ciliary muscle, leading to accommodation
PHARMACODYNAMICS Onset of action: Miosis occurs promptly
Duration: ~10-20 minutes
Thursday, January 31, 2008
Acetylcholine
U.S. BRAND NAMES — Miochol®-E
CANADIAN BRAND NAMES — Miochol®-E
THERAPEUTIC CATEGORY Cholinergic Agent, OphthalmicOphthalmic Agent, Miotic
DOSING — Ophthalmic: Adults: Instill 0.5-2 mL of 1% injection (5-20 mg)
(For additional information see "Acetylcholine: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder for solution, intraocular, as chloride: Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
GENERIC AVAILABLE — No
ADMINISTRATION — Ophthalmic: Instill into anterior chamber before or after securing one or more sutures; instillation should be gentle and parallel to the iris face and tangential to the pupil border; in cataract surgery, acetylcholine should be used only after delivery of the lens
USE — Produces complete miosis in cataract surgery, keratoplasty, iridectomy and other anterior segment surgery where rapid miosis is required
ADVERSE REACTIONS Cardiovascular: Transient bradycardia and hypotension
Central nervous system: Headache
Ocular: Iris atrophy, temporary lens opacities (attributed to osmotic effect of 5% mannitol present in preparation)
Respiratory: Dyspnea
Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to acetylcholine chloride or any component; acute iritis and acute inflammatory disease of the anterior chamber
PRECAUTIONS — Systemic effects rarely occur, but can cause problems for patients with acute CHF, bronchial asthma, peptic ulcer, hyperthyroidism, GI spasm, and urinary tract obstruction
WARNINGS — Open under aseptic conditions only
DRUG INTERACTIONS — Flurbiprofen decreases effectiveness; sodium nitrate antagonizes acetylcholine's effects
PREGNANCY RISK FACTOR — C (show table)
STABILITY — Prepare solution immediately before use; do not use solution which is not clear and colorless
MECHANISM OF ACTION — Causes contraction of the sphincter muscles of the iris, resulting in miosis and contraction of the ciliary muscle, leading to accommodation
PHARMACODYNAMICS Onset of action: Miosis occurs promptly
Duration: ~10-20 minutes
CANADIAN BRAND NAMES — Miochol®-E
THERAPEUTIC CATEGORY Cholinergic Agent, OphthalmicOphthalmic Agent, Miotic
DOSING — Ophthalmic: Adults: Instill 0.5-2 mL of 1% injection (5-20 mg)
(For additional information see "Acetylcholine: Drug information")
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder for solution, intraocular, as chloride: Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
GENERIC AVAILABLE — No
ADMINISTRATION — Ophthalmic: Instill into anterior chamber before or after securing one or more sutures; instillation should be gentle and parallel to the iris face and tangential to the pupil border; in cataract surgery, acetylcholine should be used only after delivery of the lens
USE — Produces complete miosis in cataract surgery, keratoplasty, iridectomy and other anterior segment surgery where rapid miosis is required
ADVERSE REACTIONS Cardiovascular: Transient bradycardia and hypotension
Central nervous system: Headache
Ocular: Iris atrophy, temporary lens opacities (attributed to osmotic effect of 5% mannitol present in preparation)
Respiratory: Dyspnea
Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to acetylcholine chloride or any component; acute iritis and acute inflammatory disease of the anterior chamber
PRECAUTIONS — Systemic effects rarely occur, but can cause problems for patients with acute CHF, bronchial asthma, peptic ulcer, hyperthyroidism, GI spasm, and urinary tract obstruction
WARNINGS — Open under aseptic conditions only
DRUG INTERACTIONS — Flurbiprofen decreases effectiveness; sodium nitrate antagonizes acetylcholine's effects
PREGNANCY RISK FACTOR — C (show table)
STABILITY — Prepare solution immediately before use; do not use solution which is not clear and colorless
MECHANISM OF ACTION — Causes contraction of the sphincter muscles of the iris, resulting in miosis and contraction of the ciliary muscle, leading to accommodation
PHARMACODYNAMICS Onset of action: Miosis occurs promptly
Duration: ~10-20 minutes
Acetazolamide
U.S. BRAND NAMES — Diamox® Sequels®
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
THERAPEUTIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase Inhibitor
DOSING
(For additional information see "Acetazolamide: Drug information")Children: Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/day divided every 6 hours, not to exceed 1 g/day Edema: Oral, I.V.: 5 mg/kg/dose or 150 mg/m2/dose once daily Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy
Adults: Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg once followed by 125-250 mg every 4 hours, or 500 mg sustained release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day Edema: Oral, I.V.: 250-375 mg/day Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy Altitude sickness: Oral: 500-1000 mg daily in divided doses such as 250 mg every 8-12 hours or 500 mg extended release capsules every 12-24 hours; therapy should begin 24-48 hours before and continued during ascent and for at least 48 hours after arrival at the high altitude Urine alkalinization: Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Dosing interval in renal impairment: Children and Adults: Clcr 10-50 mL/minute: Administer every 12 hours Clcr <10 mL/minute: Avoid use
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: Administer with food to decrease GI upset; tablet may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug (See Extemporaneous Preparations)
Parenteral: I.V.: Reconstitute with at least 5 mL SWI to provide a solution containing not more than 100 mg/mL; maximum concentration: 100 mg/mL; maximum rate of I.V. infusion: 500 mg/minute I.M.: Not generally recommended as the drug's alkaline pH makes it very painful
USE — Reduce elevated intraocular pressure in glaucoma; diuretic; adjunct to the treatment of refractory seizures; prevent acute altitude sickness; treatment of centrencephalic epilepsies; reduce CSF production in hydrocephalus
ADVERSE REACTIONS Cardiovascular: Cyanosis
Central nervous system: Drowsiness, ataxia, confusion, fatigue, vertigo, fever, seizures, dizziness, depression, malaise, headache, excitement
Dermatologic: Rash, erythema multiforme, photosensitivity, Stevens-Johnson syndrome (see Warnings), urticaria, toxic epidermal necrolysis
Endocrine & metabolic: Hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, hypoglycemia, growth retardation
Gastrointestinal: GI irritation, anorexia, nausea, vomiting, xerostomia, melena, dysgeusia, metallic taste, black stools
Genitourinary: Dysuria, polyuria
Hematologic: Bone marrow suppression, thrombocytopenia, hemolytic anemia, pancytopenia, agranulocytosis, leukopenia
Hepatic: Hepatic insufficiency, cholestatic jaundice, hepatic necrosis
Local: Pain at injection site
Neuromuscular & skeletal: Paresthesia, muscle weakness
Ocular: Myopia (transient)
Otic: Tinnitus
Renal: Renal calculi, phosphaturia, renal colic, hematuria, renal failure, polyuria
Respiratory: Hyperpnea
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, any component, or other sulfonamides; patients with hepatic disease or insufficiency; decreased serum sodium and/or potassium; adrenocortical insufficiency; hyperchloremic acidosis; or severe renal disease; long-term administration in patients with chronic noncongestive angle-closure glaucoma
PRECAUTIONS — Use with caution in patients with respiratory acidosis, COPD, diabetes mellitus, and gout; reduce dosage in patients with renal impairment; growth retardation has been reported in children receiving chronic therapy (possibly due to chronic acidosis)
WARNINGS — Fatalities associated with sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; discontinue use at first sign of rash or any sign of adverse reaction. Anorexia, tachypnea, lethargy, metabolic acidosis, and death have been reported in patients receiving acetazolamide and high-dose aspirin concomittantly. Tolerance to antiepileptic effects may require dosage adjustment.
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP3A4 inhibitor (weak)
Increases lithium excretion; may decrease the rate of excretion of other drugs such as procainamide, flecainide, quinidine, and tricyclic antidepressants; may increase the excretion of salicylates, amphetamine, and phenobarbital; may inactivate methenamine in the urine; may increase cyclosporine levels; may increase the risk of developing osteomalacia in patients receiving phenytoin or phenobarbital; topiramate may increase risk of nephrolithiasis and paresthesia; salicylates increase acetazolamide serum levels resulting in CNS toxicity; "high-dose" aspirin (see Warnings); ammonium chloride increases plasma concentration of nonionized acetazolamide; increased toxicity with propofol (cardiorespiratory instability); may increase effects of other folic acid antagonists
FOOD INTERACTIONS — Avoid natural licorice (causes sodium and water retention and increases potassium loss)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Serum electrolytes, CBC and platelet counts
STABILITY — Store tablets and capsules at room temperature; after reconstitution, acetazolamide injection is stable for 12 hours at room temperature and for 1 week when refrigerated; physically incompatible with parenteral multivitamins
MECHANISM OF ACTION — Competitive, reversible inhibition of the enzyme carbonic anhydrase resulting in increased renal excretion of sodium, potassium, bicarbonate, and water and decreased formation of aqueous humor; also inhibits carbonic anhydrase in CNS to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS Onset of action: Capsule, extended release: 2 hours Tablet: 1-1.5 hours I.V.: 2 minutes
Maximum effect: Capsule, extended release: 3-6 hours Tablet: 1-4 hours I.V.: 15 minutes
Duration: Capsule, extended release: 18-24 hours Tablet: 8-12 hours I.V.: 4-5 hours
PHARMACOKINETICS Absorption: Appears to be dose dependent; erratic with daily doses >10 mg/kg
Distribution: Into erythrocytes, kidneys, and breast milk (breast milk to plasma ratio of 0.25 has been reported); crosses the blood-brain barrier and the placenta
Protein binding: 95%
Half-life: 2.4-5.8 hours
Time to peak serum concentration: Tablet: 2-4 hours
Elimination: 70% to 100% of an I.V. or tablet dose and 47% of an extended release capsule excreted unchanged in urine within 24 hours
Dialysis: 20% to 50% removed by hemodialysis
TEST INTERACTIONS — May cause false-positive results for urinary protein with Albustix®, Labstix®, Albutest®, Bumintest®; interferes with HPLC method for assaying theophylline
PATIENT INFORMATION — Do not crush or chew long-acting capsule; may cause dry mouth. May rarely cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid direct exposure to sunlight; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination
(For additional information see "Acetazolamide: Patient drug information")
ADDITIONAL INFORMATION — Sodium content of 500 mg injection: 2.049 mEq
Extended release capsules are indicated only for use for the adjunctive treatment of open-angle or secondary glaucoma and the prevention of high altitude sickness; avoid using extended release capsules for anticonvulsant or diuretic therapy
Acetazolamide has been used with questionable efficacy to slow the progression of hydrocephalus in neonates and infants who may not be good candidates for surgery. I.V. or oral doses of 5 mg/kg/dose every 6 hours increased by 25 mg/kg/day to a maximum of 100 mg/kg/day, if tolerated, have been used. Furosemide was used in combination with acetazolamide (Libenson, 1999).
EXTEMPORANEOUS PREPARATIONS A 25 mg/mL suspension may be made by crushing twelve 250 mg tablets and mixing with 120 mL of a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. The resulting suspension is stable for 60 days refrigerated (Allen, 1996). When diluted in 120 mL solution of cherry syrup concentrate diluted 1:4 with simple syrup, NF, it is stable 60 days refrigerated (preferred) or at room temperature (Nahata, 2004).
A 25 mg/mL suspension may be made by crushing one hundred 250 mg tablets; add 100 mL flavor/purified water; add a mixture of 10 g Veegum (already mixed with 200 mL purified water), 300 mL 1% methylcellulose and 300 mL syrup; qsad to 1000 mL with flavor/purified water and 10 mL paraben concentrate (methylparaben 120 mg, propylparaben 12 mg, propylene glycol qsad to 100 mL); stable 79 days refrigerated (Alexander, 1991). Allen LV and Erickson MA, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids,"Am J Health Sys Pharm, 1996, 53:1944-9. Alexander KS, Haribhakti RP, and Parker GA, "Stability of Acetazolamide in Suspension Compounded From Tablets,"Am J Hosp Pharm, 1991, 48(6):1241-4. Nahata, MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
THERAPEUTIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase Inhibitor
DOSING
(For additional information see "Acetazolamide: Drug information")Children: Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/day divided every 6 hours, not to exceed 1 g/day Edema: Oral, I.V.: 5 mg/kg/dose or 150 mg/m2/dose once daily Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy
Adults: Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg once followed by 125-250 mg every 4 hours, or 500 mg sustained release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day Edema: Oral, I.V.: 250-375 mg/day Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy Altitude sickness: Oral: 500-1000 mg daily in divided doses such as 250 mg every 8-12 hours or 500 mg extended release capsules every 12-24 hours; therapy should begin 24-48 hours before and continued during ascent and for at least 48 hours after arrival at the high altitude Urine alkalinization: Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Dosing interval in renal impairment: Children and Adults: Clcr 10-50 mL/minute: Administer every 12 hours Clcr <10 mL/minute: Avoid use
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: Administer with food to decrease GI upset; tablet may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug (See Extemporaneous Preparations)
Parenteral: I.V.: Reconstitute with at least 5 mL SWI to provide a solution containing not more than 100 mg/mL; maximum concentration: 100 mg/mL; maximum rate of I.V. infusion: 500 mg/minute I.M.: Not generally recommended as the drug's alkaline pH makes it very painful
USE — Reduce elevated intraocular pressure in glaucoma; diuretic; adjunct to the treatment of refractory seizures; prevent acute altitude sickness; treatment of centrencephalic epilepsies; reduce CSF production in hydrocephalus
ADVERSE REACTIONS Cardiovascular: Cyanosis
Central nervous system: Drowsiness, ataxia, confusion, fatigue, vertigo, fever, seizures, dizziness, depression, malaise, headache, excitement
Dermatologic: Rash, erythema multiforme, photosensitivity, Stevens-Johnson syndrome (see Warnings), urticaria, toxic epidermal necrolysis
Endocrine & metabolic: Hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, hypoglycemia, growth retardation
Gastrointestinal: GI irritation, anorexia, nausea, vomiting, xerostomia, melena, dysgeusia, metallic taste, black stools
Genitourinary: Dysuria, polyuria
Hematologic: Bone marrow suppression, thrombocytopenia, hemolytic anemia, pancytopenia, agranulocytosis, leukopenia
Hepatic: Hepatic insufficiency, cholestatic jaundice, hepatic necrosis
Local: Pain at injection site
Neuromuscular & skeletal: Paresthesia, muscle weakness
Ocular: Myopia (transient)
Otic: Tinnitus
Renal: Renal calculi, phosphaturia, renal colic, hematuria, renal failure, polyuria
Respiratory: Hyperpnea
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, any component, or other sulfonamides; patients with hepatic disease or insufficiency; decreased serum sodium and/or potassium; adrenocortical insufficiency; hyperchloremic acidosis; or severe renal disease; long-term administration in patients with chronic noncongestive angle-closure glaucoma
PRECAUTIONS — Use with caution in patients with respiratory acidosis, COPD, diabetes mellitus, and gout; reduce dosage in patients with renal impairment; growth retardation has been reported in children receiving chronic therapy (possibly due to chronic acidosis)
WARNINGS — Fatalities associated with sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; discontinue use at first sign of rash or any sign of adverse reaction. Anorexia, tachypnea, lethargy, metabolic acidosis, and death have been reported in patients receiving acetazolamide and high-dose aspirin concomittantly. Tolerance to antiepileptic effects may require dosage adjustment.
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP3A4 inhibitor (weak)
Increases lithium excretion; may decrease the rate of excretion of other drugs such as procainamide, flecainide, quinidine, and tricyclic antidepressants; may increase the excretion of salicylates, amphetamine, and phenobarbital; may inactivate methenamine in the urine; may increase cyclosporine levels; may increase the risk of developing osteomalacia in patients receiving phenytoin or phenobarbital; topiramate may increase risk of nephrolithiasis and paresthesia; salicylates increase acetazolamide serum levels resulting in CNS toxicity; "high-dose" aspirin (see Warnings); ammonium chloride increases plasma concentration of nonionized acetazolamide; increased toxicity with propofol (cardiorespiratory instability); may increase effects of other folic acid antagonists
FOOD INTERACTIONS — Avoid natural licorice (causes sodium and water retention and increases potassium loss)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Serum electrolytes, CBC and platelet counts
STABILITY — Store tablets and capsules at room temperature; after reconstitution, acetazolamide injection is stable for 12 hours at room temperature and for 1 week when refrigerated; physically incompatible with parenteral multivitamins
MECHANISM OF ACTION — Competitive, reversible inhibition of the enzyme carbonic anhydrase resulting in increased renal excretion of sodium, potassium, bicarbonate, and water and decreased formation of aqueous humor; also inhibits carbonic anhydrase in CNS to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS Onset of action: Capsule, extended release: 2 hours Tablet: 1-1.5 hours I.V.: 2 minutes
Maximum effect: Capsule, extended release: 3-6 hours Tablet: 1-4 hours I.V.: 15 minutes
Duration: Capsule, extended release: 18-24 hours Tablet: 8-12 hours I.V.: 4-5 hours
PHARMACOKINETICS Absorption: Appears to be dose dependent; erratic with daily doses >10 mg/kg
Distribution: Into erythrocytes, kidneys, and breast milk (breast milk to plasma ratio of 0.25 has been reported); crosses the blood-brain barrier and the placenta
Protein binding: 95%
Half-life: 2.4-5.8 hours
Time to peak serum concentration: Tablet: 2-4 hours
Elimination: 70% to 100% of an I.V. or tablet dose and 47% of an extended release capsule excreted unchanged in urine within 24 hours
Dialysis: 20% to 50% removed by hemodialysis
TEST INTERACTIONS — May cause false-positive results for urinary protein with Albustix®, Labstix®, Albutest®, Bumintest®; interferes with HPLC method for assaying theophylline
PATIENT INFORMATION — Do not crush or chew long-acting capsule; may cause dry mouth. May rarely cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid direct exposure to sunlight; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination
(For additional information see "Acetazolamide: Patient drug information")
ADDITIONAL INFORMATION — Sodium content of 500 mg injection: 2.049 mEq
Extended release capsules are indicated only for use for the adjunctive treatment of open-angle or secondary glaucoma and the prevention of high altitude sickness; avoid using extended release capsules for anticonvulsant or diuretic therapy
Acetazolamide has been used with questionable efficacy to slow the progression of hydrocephalus in neonates and infants who may not be good candidates for surgery. I.V. or oral doses of 5 mg/kg/dose every 6 hours increased by 25 mg/kg/day to a maximum of 100 mg/kg/day, if tolerated, have been used. Furosemide was used in combination with acetazolamide (Libenson, 1999).
EXTEMPORANEOUS PREPARATIONS A 25 mg/mL suspension may be made by crushing twelve 250 mg tablets and mixing with 120 mL of a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. The resulting suspension is stable for 60 days refrigerated (Allen, 1996). When diluted in 120 mL solution of cherry syrup concentrate diluted 1:4 with simple syrup, NF, it is stable 60 days refrigerated (preferred) or at room temperature (Nahata, 2004).
A 25 mg/mL suspension may be made by crushing one hundred 250 mg tablets; add 100 mL flavor/purified water; add a mixture of 10 g Veegum (already mixed with 200 mL purified water), 300 mL 1% methylcellulose and 300 mL syrup; qsad to 1000 mL with flavor/purified water and 10 mL paraben concentrate (methylparaben 120 mg, propylparaben 12 mg, propylene glycol qsad to 100 mL); stable 79 days refrigerated (Alexander, 1991). Allen LV and Erickson MA, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids,"Am J Health Sys Pharm, 1996, 53:1944-9. Alexander KS, Haribhakti RP, and Parker GA, "Stability of Acetazolamide in Suspension Compounded From Tablets,"Am J Hosp Pharm, 1991, 48(6):1241-4. Nahata, MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
Acetazolamide
U.S. BRAND NAMES — Diamox® Sequels®
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
THERAPEUTIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase Inhibitor
DOSING
(For additional information see "Acetazolamide: Drug information")Children: Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/day divided every 6 hours, not to exceed 1 g/day Edema: Oral, I.V.: 5 mg/kg/dose or 150 mg/m2/dose once daily Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy
Adults: Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg once followed by 125-250 mg every 4 hours, or 500 mg sustained release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day Edema: Oral, I.V.: 250-375 mg/day Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy Altitude sickness: Oral: 500-1000 mg daily in divided doses such as 250 mg every 8-12 hours or 500 mg extended release capsules every 12-24 hours; therapy should begin 24-48 hours before and continued during ascent and for at least 48 hours after arrival at the high altitude Urine alkalinization: Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Dosing interval in renal impairment: Children and Adults: Clcr 10-50 mL/minute: Administer every 12 hours Clcr <10 mL/minute: Avoid use
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: Administer with food to decrease GI upset; tablet may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug (See Extemporaneous Preparations)
Parenteral: I.V.: Reconstitute with at least 5 mL SWI to provide a solution containing not more than 100 mg/mL; maximum concentration: 100 mg/mL; maximum rate of I.V. infusion: 500 mg/minute I.M.: Not generally recommended as the drug's alkaline pH makes it very painful
USE — Reduce elevated intraocular pressure in glaucoma; diuretic; adjunct to the treatment of refractory seizures; prevent acute altitude sickness; treatment of centrencephalic epilepsies; reduce CSF production in hydrocephalus
ADVERSE REACTIONS Cardiovascular: Cyanosis
Central nervous system: Drowsiness, ataxia, confusion, fatigue, vertigo, fever, seizures, dizziness, depression, malaise, headache, excitement
Dermatologic: Rash, erythema multiforme, photosensitivity, Stevens-Johnson syndrome (see Warnings), urticaria, toxic epidermal necrolysis
Endocrine & metabolic: Hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, hypoglycemia, growth retardation
Gastrointestinal: GI irritation, anorexia, nausea, vomiting, xerostomia, melena, dysgeusia, metallic taste, black stools
Genitourinary: Dysuria, polyuria
Hematologic: Bone marrow suppression, thrombocytopenia, hemolytic anemia, pancytopenia, agranulocytosis, leukopenia
Hepatic: Hepatic insufficiency, cholestatic jaundice, hepatic necrosis
Local: Pain at injection site
Neuromuscular & skeletal: Paresthesia, muscle weakness
Ocular: Myopia (transient)
Otic: Tinnitus
Renal: Renal calculi, phosphaturia, renal colic, hematuria, renal failure, polyuria
Respiratory: Hyperpnea
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, any component, or other sulfonamides; patients with hepatic disease or insufficiency; decreased serum sodium and/or potassium; adrenocortical insufficiency; hyperchloremic acidosis; or severe renal disease; long-term administration in patients with chronic noncongestive angle-closure glaucoma
PRECAUTIONS — Use with caution in patients with respiratory acidosis, COPD, diabetes mellitus, and gout; reduce dosage in patients with renal impairment; growth retardation has been reported in children receiving chronic therapy (possibly due to chronic acidosis)
WARNINGS — Fatalities associated with sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; discontinue use at first sign of rash or any sign of adverse reaction. Anorexia, tachypnea, lethargy, metabolic acidosis, and death have been reported in patients receiving acetazolamide and high-dose aspirin concomittantly. Tolerance to antiepileptic effects may require dosage adjustment.
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP3A4 inhibitor (weak)
Increases lithium excretion; may decrease the rate of excretion of other drugs such as procainamide, flecainide, quinidine, and tricyclic antidepressants; may increase the excretion of salicylates, amphetamine, and phenobarbital; may inactivate methenamine in the urine; may increase cyclosporine levels; may increase the risk of developing osteomalacia in patients receiving phenytoin or phenobarbital; topiramate may increase risk of nephrolithiasis and paresthesia; salicylates increase acetazolamide serum levels resulting in CNS toxicity; "high-dose" aspirin (see Warnings); ammonium chloride increases plasma concentration of nonionized acetazolamide; increased toxicity with propofol (cardiorespiratory instability); may increase effects of other folic acid antagonists
FOOD INTERACTIONS — Avoid natural licorice (causes sodium and water retention and increases potassium loss)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Serum electrolytes, CBC and platelet counts
STABILITY — Store tablets and capsules at room temperature; after reconstitution, acetazolamide injection is stable for 12 hours at room temperature and for 1 week when refrigerated; physically incompatible with parenteral multivitamins
MECHANISM OF ACTION — Competitive, reversible inhibition of the enzyme carbonic anhydrase resulting in increased renal excretion of sodium, potassium, bicarbonate, and water and decreased formation of aqueous humor; also inhibits carbonic anhydrase in CNS to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS Onset of action: Capsule, extended release: 2 hours Tablet: 1-1.5 hours I.V.: 2 minutes
Maximum effect: Capsule, extended release: 3-6 hours Tablet: 1-4 hours I.V.: 15 minutes
Duration: Capsule, extended release: 18-24 hours Tablet: 8-12 hours I.V.: 4-5 hours
PHARMACOKINETICS Absorption: Appears to be dose dependent; erratic with daily doses >10 mg/kg
Distribution: Into erythrocytes, kidneys, and breast milk (breast milk to plasma ratio of 0.25 has been reported); crosses the blood-brain barrier and the placenta
Protein binding: 95%
Half-life: 2.4-5.8 hours
Time to peak serum concentration: Tablet: 2-4 hours
Elimination: 70% to 100% of an I.V. or tablet dose and 47% of an extended release capsule excreted unchanged in urine within 24 hours
Dialysis: 20% to 50% removed by hemodialysis
TEST INTERACTIONS — May cause false-positive results for urinary protein with Albustix®, Labstix®, Albutest®, Bumintest®; interferes with HPLC method for assaying theophylline
PATIENT INFORMATION — Do not crush or chew long-acting capsule; may cause dry mouth. May rarely cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid direct exposure to sunlight; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination
(For additional information see "Acetazolamide: Patient drug information")
ADDITIONAL INFORMATION — Sodium content of 500 mg injection: 2.049 mEq
Extended release capsules are indicated only for use for the adjunctive treatment of open-angle or secondary glaucoma and the prevention of high altitude sickness; avoid using extended release capsules for anticonvulsant or diuretic therapy
Acetazolamide has been used with questionable efficacy to slow the progression of hydrocephalus in neonates and infants who may not be good candidates for surgery. I.V. or oral doses of 5 mg/kg/dose every 6 hours increased by 25 mg/kg/day to a maximum of 100 mg/kg/day, if tolerated, have been used. Furosemide was used in combination with acetazolamide (Libenson, 1999).
EXTEMPORANEOUS PREPARATIONS A 25 mg/mL suspension may be made by crushing twelve 250 mg tablets and mixing with 120 mL of a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. The resulting suspension is stable for 60 days refrigerated (Allen, 1996). When diluted in 120 mL solution of cherry syrup concentrate diluted 1:4 with simple syrup, NF, it is stable 60 days refrigerated (preferred) or at room temperature (Nahata, 2004).
A 25 mg/mL suspension may be made by crushing one hundred 250 mg tablets; add 100 mL flavor/purified water; add a mixture of 10 g Veegum (already mixed with 200 mL purified water), 300 mL 1% methylcellulose and 300 mL syrup; qsad to 1000 mL with flavor/purified water and 10 mL paraben concentrate (methylparaben 120 mg, propylparaben 12 mg, propylene glycol qsad to 100 mL); stable 79 days refrigerated (Alexander, 1991). Allen LV and Erickson MA, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids,"Am J Health Sys Pharm, 1996, 53:1944-9. Alexander KS, Haribhakti RP, and Parker GA, "Stability of Acetazolamide in Suspension Compounded From Tablets,"Am J Hosp Pharm, 1991, 48(6):1241-4. Nahata, MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
THERAPEUTIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase Inhibitor
DOSING
(For additional information see "Acetazolamide: Drug information")Children: Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/day divided every 6 hours, not to exceed 1 g/day Edema: Oral, I.V.: 5 mg/kg/dose or 150 mg/m2/dose once daily Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy
Adults: Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg once followed by 125-250 mg every 4 hours, or 500 mg sustained release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day Edema: Oral, I.V.: 250-375 mg/day Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy Altitude sickness: Oral: 500-1000 mg daily in divided doses such as 250 mg every 8-12 hours or 500 mg extended release capsules every 12-24 hours; therapy should begin 24-48 hours before and continued during ascent and for at least 48 hours after arrival at the high altitude Urine alkalinization: Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Dosing interval in renal impairment: Children and Adults: Clcr 10-50 mL/minute: Administer every 12 hours Clcr <10 mL/minute: Avoid use
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: Administer with food to decrease GI upset; tablet may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug (See Extemporaneous Preparations)
Parenteral: I.V.: Reconstitute with at least 5 mL SWI to provide a solution containing not more than 100 mg/mL; maximum concentration: 100 mg/mL; maximum rate of I.V. infusion: 500 mg/minute I.M.: Not generally recommended as the drug's alkaline pH makes it very painful
USE — Reduce elevated intraocular pressure in glaucoma; diuretic; adjunct to the treatment of refractory seizures; prevent acute altitude sickness; treatment of centrencephalic epilepsies; reduce CSF production in hydrocephalus
ADVERSE REACTIONS Cardiovascular: Cyanosis
Central nervous system: Drowsiness, ataxia, confusion, fatigue, vertigo, fever, seizures, dizziness, depression, malaise, headache, excitement
Dermatologic: Rash, erythema multiforme, photosensitivity, Stevens-Johnson syndrome (see Warnings), urticaria, toxic epidermal necrolysis
Endocrine & metabolic: Hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, hypoglycemia, growth retardation
Gastrointestinal: GI irritation, anorexia, nausea, vomiting, xerostomia, melena, dysgeusia, metallic taste, black stools
Genitourinary: Dysuria, polyuria
Hematologic: Bone marrow suppression, thrombocytopenia, hemolytic anemia, pancytopenia, agranulocytosis, leukopenia
Hepatic: Hepatic insufficiency, cholestatic jaundice, hepatic necrosis
Local: Pain at injection site
Neuromuscular & skeletal: Paresthesia, muscle weakness
Ocular: Myopia (transient)
Otic: Tinnitus
Renal: Renal calculi, phosphaturia, renal colic, hematuria, renal failure, polyuria
Respiratory: Hyperpnea
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, any component, or other sulfonamides; patients with hepatic disease or insufficiency; decreased serum sodium and/or potassium; adrenocortical insufficiency; hyperchloremic acidosis; or severe renal disease; long-term administration in patients with chronic noncongestive angle-closure glaucoma
PRECAUTIONS — Use with caution in patients with respiratory acidosis, COPD, diabetes mellitus, and gout; reduce dosage in patients with renal impairment; growth retardation has been reported in children receiving chronic therapy (possibly due to chronic acidosis)
WARNINGS — Fatalities associated with sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; discontinue use at first sign of rash or any sign of adverse reaction. Anorexia, tachypnea, lethargy, metabolic acidosis, and death have been reported in patients receiving acetazolamide and high-dose aspirin concomittantly. Tolerance to antiepileptic effects may require dosage adjustment.
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP3A4 inhibitor (weak)
Increases lithium excretion; may decrease the rate of excretion of other drugs such as procainamide, flecainide, quinidine, and tricyclic antidepressants; may increase the excretion of salicylates, amphetamine, and phenobarbital; may inactivate methenamine in the urine; may increase cyclosporine levels; may increase the risk of developing osteomalacia in patients receiving phenytoin or phenobarbital; topiramate may increase risk of nephrolithiasis and paresthesia; salicylates increase acetazolamide serum levels resulting in CNS toxicity; "high-dose" aspirin (see Warnings); ammonium chloride increases plasma concentration of nonionized acetazolamide; increased toxicity with propofol (cardiorespiratory instability); may increase effects of other folic acid antagonists
FOOD INTERACTIONS — Avoid natural licorice (causes sodium and water retention and increases potassium loss)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Serum electrolytes, CBC and platelet counts
STABILITY — Store tablets and capsules at room temperature; after reconstitution, acetazolamide injection is stable for 12 hours at room temperature and for 1 week when refrigerated; physically incompatible with parenteral multivitamins
MECHANISM OF ACTION — Competitive, reversible inhibition of the enzyme carbonic anhydrase resulting in increased renal excretion of sodium, potassium, bicarbonate, and water and decreased formation of aqueous humor; also inhibits carbonic anhydrase in CNS to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS Onset of action: Capsule, extended release: 2 hours Tablet: 1-1.5 hours I.V.: 2 minutes
Maximum effect: Capsule, extended release: 3-6 hours Tablet: 1-4 hours I.V.: 15 minutes
Duration: Capsule, extended release: 18-24 hours Tablet: 8-12 hours I.V.: 4-5 hours
PHARMACOKINETICS Absorption: Appears to be dose dependent; erratic with daily doses >10 mg/kg
Distribution: Into erythrocytes, kidneys, and breast milk (breast milk to plasma ratio of 0.25 has been reported); crosses the blood-brain barrier and the placenta
Protein binding: 95%
Half-life: 2.4-5.8 hours
Time to peak serum concentration: Tablet: 2-4 hours
Elimination: 70% to 100% of an I.V. or tablet dose and 47% of an extended release capsule excreted unchanged in urine within 24 hours
Dialysis: 20% to 50% removed by hemodialysis
TEST INTERACTIONS — May cause false-positive results for urinary protein with Albustix®, Labstix®, Albutest®, Bumintest®; interferes with HPLC method for assaying theophylline
PATIENT INFORMATION — Do not crush or chew long-acting capsule; may cause dry mouth. May rarely cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid direct exposure to sunlight; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination
(For additional information see "Acetazolamide: Patient drug information")
ADDITIONAL INFORMATION — Sodium content of 500 mg injection: 2.049 mEq
Extended release capsules are indicated only for use for the adjunctive treatment of open-angle or secondary glaucoma and the prevention of high altitude sickness; avoid using extended release capsules for anticonvulsant or diuretic therapy
Acetazolamide has been used with questionable efficacy to slow the progression of hydrocephalus in neonates and infants who may not be good candidates for surgery. I.V. or oral doses of 5 mg/kg/dose every 6 hours increased by 25 mg/kg/day to a maximum of 100 mg/kg/day, if tolerated, have been used. Furosemide was used in combination with acetazolamide (Libenson, 1999).
EXTEMPORANEOUS PREPARATIONS A 25 mg/mL suspension may be made by crushing twelve 250 mg tablets and mixing with 120 mL of a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. The resulting suspension is stable for 60 days refrigerated (Allen, 1996). When diluted in 120 mL solution of cherry syrup concentrate diluted 1:4 with simple syrup, NF, it is stable 60 days refrigerated (preferred) or at room temperature (Nahata, 2004).
A 25 mg/mL suspension may be made by crushing one hundred 250 mg tablets; add 100 mL flavor/purified water; add a mixture of 10 g Veegum (already mixed with 200 mL purified water), 300 mL 1% methylcellulose and 300 mL syrup; qsad to 1000 mL with flavor/purified water and 10 mL paraben concentrate (methylparaben 120 mg, propylparaben 12 mg, propylene glycol qsad to 100 mL); stable 79 days refrigerated (Alexander, 1991). Allen LV and Erickson MA, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids,"Am J Health Sys Pharm, 1996, 53:1944-9. Alexander KS, Haribhakti RP, and Parker GA, "Stability of Acetazolamide in Suspension Compounded From Tablets,"Am J Hosp Pharm, 1991, 48(6):1241-4. Nahata, MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
Acetaminophen and codeine
U.S. BRAND NAMES — Capital® and Codeine; Tylenol® With Codeine
CANADIAN BRAND NAMES — ratio-Emtec; ratio-Lenoltec; Triatec-30; Triatec-8 Strong; Triatec-8; Tylenol Elixir with Codeine; Tylenol No. 1 Forte; Tylenol No. 1; Tylenol No. 2 with Codeine; Tylenol No. 3 with Codeine; Tylenol No. 4 with Codeine
SYNONYMS — Codeine and Acetaminophen
THERAPEUTIC CATEGORY Analgesic, Narcotic
DOSING — Oral (doses should be titrated to appropriate analgesic effect):
(For additional information see "Acetaminophen and codeine: Drug information")
Children: Analgesic: 0.5-1 mg codeine/kg/dose every 4-6 hours 3-6 years: 5 mL 3-4 times/day as needed 7-12 years: 10 mL 3-4 times/day as needed >12 years: 15 mL every 4 hours as needed
Adults: 1-2 tablets every 4 hours; maximum dose: 12 tablets/24 hours
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product; [CAN] = Canadian brand name
Caplet: ratio-Lenoltec No. 1 [CAN], Tylenol No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] Tylenol No. 1 Forte [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.]
Elixir, oral [C-V]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (5 mL, 10 mL, 12.5 mL, 15 mL, 120 mL, 480 mL) [contains alcohol 7%] Tylenol® with Codeine [DSC]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [contains alcohol 7%; cherry flavor] Tylenol Elixir with Codeine [CAN]: Acetaminophen 160 mg and codeine phosphate 8 mg per 5 mL (500 mL) [contains alcohol 7%, sucrose 31%; cherry flavor; not available in the U.S.]
Suspension, oral [C-V] (Capital® and Codeine): Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [alcohol free; fruit punch flavor]
Tablet [C-III]: Acetaminophen 300 mg and codeine phosphate 15 mg; acetaminophen 300 mg and codeine phosphate 30 mg; acetaminophen 300 mg and codeine phosphate 60 mg ratio-Emtec [CAN], Triatec-30 [CAN]: Acetaminophen 300 mg and codeine phosphate 30 mg [not available in the U.S.] ratio-Lenoltec No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 2 [CAN], Tylenol No. 2 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 15 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 3 [CAN], Tylenol No. 3 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 30 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 4 [CAN], Tylenol No. 4 with Codeine [CAN]: Acetaminophen 300 mg and codeine phosphate 60 mg [not available in the U.S.] Triatec-8 [CAN]: Acetaminophen 325 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Triatec-8 Strong [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Tylenol® with Codeine No. 3: Acetaminophen 300 mg and codeine phosphate 30 mg [contains sodium metabisulfite] Tylenol® with Codeine No. 4: Acetaminophen 300 mg and codeine phosphate 60 mg [contains sodium metabisulfite]
GENERIC AVAILABLE — Yes
ADMINISTRATION — Oral: Administer with food to decrease GI upset; shake suspension well before use
USE — Relief of mild to moderate pain
ADVERSE REACTIONS Acetaminophen: Dermatologic: Rash Hematologic: Blood dyscrasias (neutropenia, pancytopenia, leukopenia) Hepatic: Hepatic necrosis with overdose Renal: Renal injury with chronic use Miscellaneous: Hypersensitivity reactions (rare)
Codeine: Cardiovascular: Palpitations, hypotension, bradycardia, peripheral vasodilation Central nervous system: CNS depression, dizziness, drowsiness, sedation, elevated intracranial pressure Dermatologic: Pruritus Endocrine & metabolic: Antidiuretic hormone release Gastrointestinal: Nausea, vomiting, constipation, biliary tract spasm Genitourinary: Urinary retention Ocular: Miosis Respiratory: Respiratory depression Miscellaneous: Histamine release, physical and psychological dependence with prolonged use
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine phosphate, or any component (see Warnings)
PRECAUTIONS — Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (morphine, hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone) or respiratory disease/compromise.
G-6-PD deficiency: Although several case reports of acetaminophen-associated hemolytic anemia have been reported in patients with G-6-PD deficiency, a direct cause and effect relationship has not been well established (concurrent illnesses such as fever or infection may precipitate hemolytic anemia in patients with G-6-PD deficiency); therefore, acetaminophen is generally thought to be safe when given in therapeutic doses to patients with G-6-PD deficiency.
WARNINGS — Some tablets contain metabisulfite which may cause allergic reactions in susceptible individuals. Elixir may contain sodium benzoate; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse; avoid use of acetaminophen and codeine products containing sodium benzoate in neonates; in vitro and animal studies have shown that benzoate displaces bilirubin from protein binding sites
RESTRICTIONS — C-III; C-V
DRUG INTERACTIONS — See Acetaminophen and Codeine
FOOD INTERACTIONS — Rate of absorption of acetaminophen may be decreased when given with food high in carbohydrates
PREGNANCY RISK FACTOR — C (show table)
MECHANISM OF ACTION — See individual monographs for Acetaminophen and Codeine
PHARMACOKINETICS — See individual monographs for Acetaminophen and Codeine
PATIENT INFORMATION — Codeine may be habit-forming; avoid abrupt discontinuation after prolonged use; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination; avoid alcohol
(For additional information see "Acetaminophen and codeine: Patient drug information")
NURSING IMPLICATIONS — Observe patient for excessive sedation, respiratory depression
ADDITIONAL INFORMATION — Tylenol® With Codeine elixir contains saccharin
CANADIAN BRAND NAMES — ratio-Emtec; ratio-Lenoltec; Triatec-30; Triatec-8 Strong; Triatec-8; Tylenol Elixir with Codeine; Tylenol No. 1 Forte; Tylenol No. 1; Tylenol No. 2 with Codeine; Tylenol No. 3 with Codeine; Tylenol No. 4 with Codeine
SYNONYMS — Codeine and Acetaminophen
THERAPEUTIC CATEGORY Analgesic, Narcotic
DOSING — Oral (doses should be titrated to appropriate analgesic effect):
(For additional information see "Acetaminophen and codeine: Drug information")
Children: Analgesic: 0.5-1 mg codeine/kg/dose every 4-6 hours 3-6 years: 5 mL 3-4 times/day as needed 7-12 years: 10 mL 3-4 times/day as needed >12 years: 15 mL every 4 hours as needed
Adults: 1-2 tablets every 4 hours; maximum dose: 12 tablets/24 hours
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product; [CAN] = Canadian brand name
Caplet: ratio-Lenoltec No. 1 [CAN], Tylenol No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] Tylenol No. 1 Forte [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.]
Elixir, oral [C-V]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (5 mL, 10 mL, 12.5 mL, 15 mL, 120 mL, 480 mL) [contains alcohol 7%] Tylenol® with Codeine [DSC]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [contains alcohol 7%; cherry flavor] Tylenol Elixir with Codeine [CAN]: Acetaminophen 160 mg and codeine phosphate 8 mg per 5 mL (500 mL) [contains alcohol 7%, sucrose 31%; cherry flavor; not available in the U.S.]
Suspension, oral [C-V] (Capital® and Codeine): Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [alcohol free; fruit punch flavor]
Tablet [C-III]: Acetaminophen 300 mg and codeine phosphate 15 mg; acetaminophen 300 mg and codeine phosphate 30 mg; acetaminophen 300 mg and codeine phosphate 60 mg ratio-Emtec [CAN], Triatec-30 [CAN]: Acetaminophen 300 mg and codeine phosphate 30 mg [not available in the U.S.] ratio-Lenoltec No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 2 [CAN], Tylenol No. 2 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 15 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 3 [CAN], Tylenol No. 3 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 30 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 4 [CAN], Tylenol No. 4 with Codeine [CAN]: Acetaminophen 300 mg and codeine phosphate 60 mg [not available in the U.S.] Triatec-8 [CAN]: Acetaminophen 325 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Triatec-8 Strong [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Tylenol® with Codeine No. 3: Acetaminophen 300 mg and codeine phosphate 30 mg [contains sodium metabisulfite] Tylenol® with Codeine No. 4: Acetaminophen 300 mg and codeine phosphate 60 mg [contains sodium metabisulfite]
GENERIC AVAILABLE — Yes
ADMINISTRATION — Oral: Administer with food to decrease GI upset; shake suspension well before use
USE — Relief of mild to moderate pain
ADVERSE REACTIONS Acetaminophen: Dermatologic: Rash Hematologic: Blood dyscrasias (neutropenia, pancytopenia, leukopenia) Hepatic: Hepatic necrosis with overdose Renal: Renal injury with chronic use Miscellaneous: Hypersensitivity reactions (rare)
Codeine: Cardiovascular: Palpitations, hypotension, bradycardia, peripheral vasodilation Central nervous system: CNS depression, dizziness, drowsiness, sedation, elevated intracranial pressure Dermatologic: Pruritus Endocrine & metabolic: Antidiuretic hormone release Gastrointestinal: Nausea, vomiting, constipation, biliary tract spasm Genitourinary: Urinary retention Ocular: Miosis Respiratory: Respiratory depression Miscellaneous: Histamine release, physical and psychological dependence with prolonged use
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine phosphate, or any component (see Warnings)
PRECAUTIONS — Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (morphine, hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone) or respiratory disease/compromise.
G-6-PD deficiency: Although several case reports of acetaminophen-associated hemolytic anemia have been reported in patients with G-6-PD deficiency, a direct cause and effect relationship has not been well established (concurrent illnesses such as fever or infection may precipitate hemolytic anemia in patients with G-6-PD deficiency); therefore, acetaminophen is generally thought to be safe when given in therapeutic doses to patients with G-6-PD deficiency.
WARNINGS — Some tablets contain metabisulfite which may cause allergic reactions in susceptible individuals. Elixir may contain sodium benzoate; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse; avoid use of acetaminophen and codeine products containing sodium benzoate in neonates; in vitro and animal studies have shown that benzoate displaces bilirubin from protein binding sites
RESTRICTIONS — C-III; C-V
DRUG INTERACTIONS — See Acetaminophen and Codeine
FOOD INTERACTIONS — Rate of absorption of acetaminophen may be decreased when given with food high in carbohydrates
PREGNANCY RISK FACTOR — C (show table)
MECHANISM OF ACTION — See individual monographs for Acetaminophen and Codeine
PHARMACOKINETICS — See individual monographs for Acetaminophen and Codeine
PATIENT INFORMATION — Codeine may be habit-forming; avoid abrupt discontinuation after prolonged use; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination; avoid alcohol
(For additional information see "Acetaminophen and codeine: Patient drug information")
NURSING IMPLICATIONS — Observe patient for excessive sedation, respiratory depression
ADDITIONAL INFORMATION — Tylenol® With Codeine elixir contains saccharin
Acetaminophen and codeine
U.S. BRAND NAMES — Capital® and Codeine; Tylenol® With Codeine
CANADIAN BRAND NAMES — ratio-Emtec; ratio-Lenoltec; Triatec-30; Triatec-8 Strong; Triatec-8; Tylenol Elixir with Codeine; Tylenol No. 1 Forte; Tylenol No. 1; Tylenol No. 2 with Codeine; Tylenol No. 3 with Codeine; Tylenol No. 4 with Codeine
SYNONYMS — Codeine and Acetaminophen
THERAPEUTIC CATEGORY Analgesic, Narcotic
DOSING — Oral (doses should be titrated to appropriate analgesic effect):
(For additional information see "Acetaminophen and codeine: Drug information")
Children: Analgesic: 0.5-1 mg codeine/kg/dose every 4-6 hours 3-6 years: 5 mL 3-4 times/day as needed 7-12 years: 10 mL 3-4 times/day as needed >12 years: 15 mL every 4 hours as needed
Adults: 1-2 tablets every 4 hours; maximum dose: 12 tablets/24 hours
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product; [CAN] = Canadian brand name
Caplet: ratio-Lenoltec No. 1 [CAN], Tylenol No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] Tylenol No. 1 Forte [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.]
Elixir, oral [C-V]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (5 mL, 10 mL, 12.5 mL, 15 mL, 120 mL, 480 mL) [contains alcohol 7%] Tylenol® with Codeine [DSC]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [contains alcohol 7%; cherry flavor] Tylenol Elixir with Codeine [CAN]: Acetaminophen 160 mg and codeine phosphate 8 mg per 5 mL (500 mL) [contains alcohol 7%, sucrose 31%; cherry flavor; not available in the U.S.]
Suspension, oral [C-V] (Capital® and Codeine): Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [alcohol free; fruit punch flavor]
Tablet [C-III]: Acetaminophen 300 mg and codeine phosphate 15 mg; acetaminophen 300 mg and codeine phosphate 30 mg; acetaminophen 300 mg and codeine phosphate 60 mg ratio-Emtec [CAN], Triatec-30 [CAN]: Acetaminophen 300 mg and codeine phosphate 30 mg [not available in the U.S.] ratio-Lenoltec No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 2 [CAN], Tylenol No. 2 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 15 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 3 [CAN], Tylenol No. 3 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 30 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 4 [CAN], Tylenol No. 4 with Codeine [CAN]: Acetaminophen 300 mg and codeine phosphate 60 mg [not available in the U.S.] Triatec-8 [CAN]: Acetaminophen 325 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Triatec-8 Strong [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Tylenol® with Codeine No. 3: Acetaminophen 300 mg and codeine phosphate 30 mg [contains sodium metabisulfite] Tylenol® with Codeine No. 4: Acetaminophen 300 mg and codeine phosphate 60 mg [contains sodium metabisulfite]
GENERIC AVAILABLE — Yes
ADMINISTRATION — Oral: Administer with food to decrease GI upset; shake suspension well before use
USE — Relief of mild to moderate pain
ADVERSE REACTIONS Acetaminophen: Dermatologic: Rash Hematologic: Blood dyscrasias (neutropenia, pancytopenia, leukopenia) Hepatic: Hepatic necrosis with overdose Renal: Renal injury with chronic use Miscellaneous: Hypersensitivity reactions (rare)
Codeine: Cardiovascular: Palpitations, hypotension, bradycardia, peripheral vasodilation Central nervous system: CNS depression, dizziness, drowsiness, sedation, elevated intracranial pressure Dermatologic: Pruritus Endocrine & metabolic: Antidiuretic hormone release Gastrointestinal: Nausea, vomiting, constipation, biliary tract spasm Genitourinary: Urinary retention Ocular: Miosis Respiratory: Respiratory depression Miscellaneous: Histamine release, physical and psychological dependence with prolonged use
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine phosphate, or any component (see Warnings)
PRECAUTIONS — Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (morphine, hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone) or respiratory disease/compromise.
G-6-PD deficiency: Although several case reports of acetaminophen-associated hemolytic anemia have been reported in patients with G-6-PD deficiency, a direct cause and effect relationship has not been well established (concurrent illnesses such as fever or infection may precipitate hemolytic anemia in patients with G-6-PD deficiency); therefore, acetaminophen is generally thought to be safe when given in therapeutic doses to patients with G-6-PD deficiency.
WARNINGS — Some tablets contain metabisulfite which may cause allergic reactions in susceptible individuals. Elixir may contain sodium benzoate; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse; avoid use of acetaminophen and codeine products containing sodium benzoate in neonates; in vitro and animal studies have shown that benzoate displaces bilirubin from protein binding sites
RESTRICTIONS — C-III; C-V
DRUG INTERACTIONS — See Acetaminophen and Codeine
FOOD INTERACTIONS — Rate of absorption of acetaminophen may be decreased when given with food high in carbohydrates
PREGNANCY RISK FACTOR — C (show table)
MECHANISM OF ACTION — See individual monographs for Acetaminophen and Codeine
PHARMACOKINETICS — See individual monographs for Acetaminophen and Codeine
PATIENT INFORMATION — Codeine may be habit-forming; avoid abrupt discontinuation after prolonged use; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination; avoid alcohol
(For additional information see "Acetaminophen and codeine: Patient drug information")
NURSING IMPLICATIONS — Observe patient for excessive sedation, respiratory depression
ADDITIONAL INFORMATION — Tylenol® With Codeine elixir contains saccharin
CANADIAN BRAND NAMES — ratio-Emtec; ratio-Lenoltec; Triatec-30; Triatec-8 Strong; Triatec-8; Tylenol Elixir with Codeine; Tylenol No. 1 Forte; Tylenol No. 1; Tylenol No. 2 with Codeine; Tylenol No. 3 with Codeine; Tylenol No. 4 with Codeine
SYNONYMS — Codeine and Acetaminophen
THERAPEUTIC CATEGORY Analgesic, Narcotic
DOSING — Oral (doses should be titrated to appropriate analgesic effect):
(For additional information see "Acetaminophen and codeine: Drug information")
Children: Analgesic: 0.5-1 mg codeine/kg/dose every 4-6 hours 3-6 years: 5 mL 3-4 times/day as needed 7-12 years: 10 mL 3-4 times/day as needed >12 years: 15 mL every 4 hours as needed
Adults: 1-2 tablets every 4 hours; maximum dose: 12 tablets/24 hours
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product; [CAN] = Canadian brand name
Caplet: ratio-Lenoltec No. 1 [CAN], Tylenol No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] Tylenol No. 1 Forte [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.]
Elixir, oral [C-V]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (5 mL, 10 mL, 12.5 mL, 15 mL, 120 mL, 480 mL) [contains alcohol 7%] Tylenol® with Codeine [DSC]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [contains alcohol 7%; cherry flavor] Tylenol Elixir with Codeine [CAN]: Acetaminophen 160 mg and codeine phosphate 8 mg per 5 mL (500 mL) [contains alcohol 7%, sucrose 31%; cherry flavor; not available in the U.S.]
Suspension, oral [C-V] (Capital® and Codeine): Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [alcohol free; fruit punch flavor]
Tablet [C-III]: Acetaminophen 300 mg and codeine phosphate 15 mg; acetaminophen 300 mg and codeine phosphate 30 mg; acetaminophen 300 mg and codeine phosphate 60 mg ratio-Emtec [CAN], Triatec-30 [CAN]: Acetaminophen 300 mg and codeine phosphate 30 mg [not available in the U.S.] ratio-Lenoltec No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 2 [CAN], Tylenol No. 2 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 15 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 3 [CAN], Tylenol No. 3 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 30 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 4 [CAN], Tylenol No. 4 with Codeine [CAN]: Acetaminophen 300 mg and codeine phosphate 60 mg [not available in the U.S.] Triatec-8 [CAN]: Acetaminophen 325 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Triatec-8 Strong [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Tylenol® with Codeine No. 3: Acetaminophen 300 mg and codeine phosphate 30 mg [contains sodium metabisulfite] Tylenol® with Codeine No. 4: Acetaminophen 300 mg and codeine phosphate 60 mg [contains sodium metabisulfite]
GENERIC AVAILABLE — Yes
ADMINISTRATION — Oral: Administer with food to decrease GI upset; shake suspension well before use
USE — Relief of mild to moderate pain
ADVERSE REACTIONS Acetaminophen: Dermatologic: Rash Hematologic: Blood dyscrasias (neutropenia, pancytopenia, leukopenia) Hepatic: Hepatic necrosis with overdose Renal: Renal injury with chronic use Miscellaneous: Hypersensitivity reactions (rare)
Codeine: Cardiovascular: Palpitations, hypotension, bradycardia, peripheral vasodilation Central nervous system: CNS depression, dizziness, drowsiness, sedation, elevated intracranial pressure Dermatologic: Pruritus Endocrine & metabolic: Antidiuretic hormone release Gastrointestinal: Nausea, vomiting, constipation, biliary tract spasm Genitourinary: Urinary retention Ocular: Miosis Respiratory: Respiratory depression Miscellaneous: Histamine release, physical and psychological dependence with prolonged use
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine phosphate, or any component (see Warnings)
PRECAUTIONS — Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (morphine, hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone) or respiratory disease/compromise.
G-6-PD deficiency: Although several case reports of acetaminophen-associated hemolytic anemia have been reported in patients with G-6-PD deficiency, a direct cause and effect relationship has not been well established (concurrent illnesses such as fever or infection may precipitate hemolytic anemia in patients with G-6-PD deficiency); therefore, acetaminophen is generally thought to be safe when given in therapeutic doses to patients with G-6-PD deficiency.
WARNINGS — Some tablets contain metabisulfite which may cause allergic reactions in susceptible individuals. Elixir may contain sodium benzoate; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse; avoid use of acetaminophen and codeine products containing sodium benzoate in neonates; in vitro and animal studies have shown that benzoate displaces bilirubin from protein binding sites
RESTRICTIONS — C-III; C-V
DRUG INTERACTIONS — See Acetaminophen and Codeine
FOOD INTERACTIONS — Rate of absorption of acetaminophen may be decreased when given with food high in carbohydrates
PREGNANCY RISK FACTOR — C (show table)
MECHANISM OF ACTION — See individual monographs for Acetaminophen and Codeine
PHARMACOKINETICS — See individual monographs for Acetaminophen and Codeine
PATIENT INFORMATION — Codeine may be habit-forming; avoid abrupt discontinuation after prolonged use; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination; avoid alcohol
(For additional information see "Acetaminophen and codeine: Patient drug information")
NURSING IMPLICATIONS — Observe patient for excessive sedation, respiratory depression
ADDITIONAL INFORMATION — Tylenol® With Codeine elixir contains saccharin
Acetaminophen
U.S. BRAND NAMES — Acephen™ [OTC]; Apra Children's [OTC]; Aspirin Free Anacin® Maximum Strength [OTC]; Cetafen Extra® [OTC]; Cetafen® [OTC]; Comtrex® Sore Throat Maximum Strength [OTC]; FeverALL® [OTC]; Genapap™ Children [OTC]; Genapap™ Extra Strength [OTC]; Genapap™ Infant [OTC]; Genapap™ [OTC]; Genebs Extra Strength [OTC]; Genebs [OTC]; Infantaire [OTC]; Mapap Children's [OTC]; Mapap Extra Strength [OTC]; Mapap Infants [OTC]; Mapap [OTC]; Nortemp Children's [OTC]; Pain Eze [OTC]; Silapap® Children's [OTC]; Silapap® Infants [OTC]; Tycolene Maximum Strength [OTC]; Tycolene [OTC]; Tylenol® 8 Hour [OTC]; Tylenol® Arthritis Pain [OTC]; Tylenol® Children's with Flavor Creator [OTC]; Tylenol® Children's [OTC]; Tylenol® Extra Strength [OTC]; Tylenol® Infants [OTC]; Tylenol® Junior [OTC]; Tylenol® [OTC]; Valorin Extra [OTC]; Valorin [OTC]
CANADIAN BRAND NAMES — Abenol®; Apo-Acetaminophen®; Atasol®; Novo-Gesic; Pediatrix; Tempra®; Tylenol®
SYNONYMS — APAP; N-Acetyl-P-Aminophenol; Paracetamol
THERAPEUTIC CATEGORY Analgesic, Non-narcoticAntipyretic
DOSING
(For additional information see "Acetaminophen: Drug information")Neonates: Oral, rectal: 10-15 mg/kg/dose every 6-8 hours as needed International Evidence-Based Group for Neonatal Pain recommendations (Anand, 2001; Anand, 2002): Preterm infants 28-32 weeks: Oral: 10-12 mg/kg/dose every 6-8 hours; maximum daily dose: 40 mg/kg/day Rectal: 20 mg/kg/dose every 12 hours; maximum daily dose: 40 mg/kg/day Preterm infants 32-36 weeks and term infants <10 days: Oral: 10-15 mg/kg/dose every 6 hours; maximum daily dose: 60 mg/kg/day Rectal: Loading dose: 30 mg/kg; then 15 mg/kg/dose every 8 hours; maximum daily dose: 60 mg/kg/day Term infants 10 days: Oral: 10-15 mg/kg/dose every 4-6 hours; maximum daily dose: 90 mg/kg/day Rectal: Loading dose: 30 mg/kg; then 20 mg/kg/dose every 6-8 hours; maximum daily dose: 90 mg/kg/day
Infants and Children: Oral: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses in 24 hours; alternatively, the following doses may be used.
Alternative Acetaminophen Dosing (Oral)1: 6-11 lbs: 0-3 months: 40 mg 12-17 lbs: 4-11 months: 80 mg 18-23 lbs: 1-2 years: 120 mg 24-35 lbs: 2-3 years: 160 mg 36-47 lbs: 4-5 years: 240 mg 48-59 lbs: 6-8 years: 320 mg 60-71 lbs: 9-10 years: 400 mg 72-95 lbs: 11 years: 480 mg 1Manufacturer's recommendations; use of weight to select dose is preferred; if weight is not available, then use age Rectal: 10-20 mg/kg/dose every 4-6 hours as needed. Note: Although the perioperative use of high-dose rectal acetaminophen (eg, 25-45 mg/kg/dose) has been investigated in several studies, its routine use remains controversial; optimal doses and dosing frequency to ensure efficacy and safety have not yet been established; further studies are needed (see Buck, 2001).
Children 12 years and Adults: Oral, rectal: 325-650 mg every 4-6 hours or 1000 mg 3-4 times/day; do not exceed 4 g/day
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet: 500 mg Cetafen Extra® Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Tycolene Maximum Strength, Tylenol® Extra Strength: 500 mg
Caplet, extended release: Tylenol® 8 Hour, Tylenol® Arthritis Pain: 650 mg
Capsule: 500 mg
Elixir: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) Apra Children's: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) [alcohol free; contains benzoic acid; cherry and grape flavors] Mapap Children's: 160 mg/5 mL (120 mL) [alcohol free; contains benzoic acid and sodium benzoate; cherry flavor]
Gelcap: Mapap Extra Strength, Tylenol® Extra Strength: 500 mg
Geltab: Tylenol® Extra Strength: 500 mg
Geltab, extended release: Tylenol® 8 Hour: 650 mg [DSC]
Liquid, oral: 500 mg/15 mL (240 mL) Comtrex® Sore Throat Maximum Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; honey lemon flavor] Genapap™ Children: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry and grape flavors] Silapap®: 160 mg/5 mL (120 mL, 240 mL, 480 mL) [sugar free; contains sodium benzoate; cherry flavor] Tylenol® Extra Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; cherry flavor]
Solution, oral: 160 mg/5 mL (120 mL, 480 mL)
Solution, oral [drops]: 80 mg/0.8 mL (15 mL) [droppers are marked at 0.4 mL (40 mg) and at 0.8 mL (80 mg)] Genapap™ Infant: 80 mg/0.8 mL (15 mL) [fruit flavor] Infantaire: 80 mg/0.8mL (15 mL, 30 mL) Silapap® Infant's: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor]
Suppository, rectal: 120 mg, 325 mg, 650 mg Acephen™: 120 mg, 325 mg, 650 mg FeverALL®: 80 mg, 120 mg, 325 mg, 650 mg Mapap: 125 mg, 650 mg
Suspension, oral: Mapap Children's: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry flavor] Nortemp Children's: 160 mg/5 mL (120 mL) [alcohol free; contains sodium benzoate; cotton candy flavor] Tylenol® Children's: 160 mg/5 mL (120 mL, 240 mL) [contains sodium benzoate; bubble gum yum, cherry blast, dye free cherry, grape splash, and very berry strawberry flavors] Tylenol® Children's with Flavor Creator: 160 mg/5 mL (120 mL) [contains sodium 2 mg/5 mL and sodium benzoate; cherry blast flavor; packaged with apple (4), bubblegum (8), chocolate (4), & strawberry (4) sugar free flavor packets]
Suspension, oral [drops]: Mapap Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor] Tylenol® Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry, dye free cherry, and grape flavors]
Tablet: 325 mg, 500 mg Aspirin Free Anacin® Extra Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Pain Eze, Tylenol® Extra Strength, Valorin Extra: 500 mg Cetafen®, Genapap™, Genebs, Mapap, Tycolene, Tylenol®, Valorin: 325 mg
Tablet, chewable: 80 mg Genapap™ Children: 80 mg [contains phenylalanine 6 mg/tablet; fruit and grape flavors] Mapap Children's: 80 mg [contains phenylalanine 3 mg/tablet; bubble gum, fruit, and grape flavors] Mapap Junior Strength: 160 mg [contains phenylalanine 12 mg/tablet; grape flavor]
Tablet, orally disintegrating: 80 mg, 160 mg Tylenol® Children's Meltaways: 80 mg [bubble gum, grape, and watermelon flavors] Tylenol® Junior Meltaways: 160 mg [bubble gum and grape flavors]
GENERIC AVAILABLE — Yes: Excludes extended release products
ADMINISTRATION — Oral: Administer with food to decrease GI upset; shake suspension well before use; do not crush or chew extended release products
USE — Treatment of mild to moderate pain and fever; does not have antirheumatic or systemic anti-inflammatory effects
ADVERSE REACTIONS Dermatologic: Rash
Hematologic: Blood dyscrasias (neutropenia, pancytopenia, leukopenia)
Hepatic: Hepatic necrosis with overdose
Renal: Renal injury with chronic use
Miscellaneous: Hypersensitivity reactions (rare)
CONTRAINDICATIONS — Hypersensitivity to acetaminophen or any component
PRECAUTIONS — Some products (eg, chewable tablets) contain aspartame which is metabolized to phenylalanine and must be avoided (or used with caution) in patients with phenylketonuria.
G-6-PD deficiency: Although several case reports of acetaminophen-associated hemolytic anemia have been reported in patients with G-6-PD deficiency, a direct cause and effect relationship has not been well established (concurrent illnesses such as fever or infection may precipitate hemolytic anemia in patients with G-6-PD deficiency); therefore, acetaminophen is generally thought to be safe when given in therapeutic doses to patients with G-6-PD deficiency.
WARNINGS — May cause severe hepatic toxicity with overdose. Use with caution in patients with alcoholic liver disease. Chronic daily dosing in adults of 5-8 g of acetaminophen over several weeks or 3-4 g/day for 1 year have resulted in liver damage. Do not exceed maximum daily doses; consider acetaminophen content of combination products when evaluating the dose of acetaminophen.
Some elixir preparations contain benzoic acid; liquid preparations (ie, elixir, liquid, suspension, and drops) may contain sodium benzoate (see Dosage Forms); benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse; avoid use of acetaminophen products containing sodium benzoate in neonates; in vitro and animal studies have shown that benzoate displaces bilirubin from protein binding sites
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP1A2 substrate (minor), CYP2A6, CYP2C9, CYP2D6, CYP2E1 and CYP3A3/4 isoenzyme substrate
Enzyme inducers (barbiturates, carbamazepine, phenytoin, rifampin), carmustine (with high dose acetaminophen), isoniazid, alcohol (especially chronic use) can increase hepatotoxicity; rifampin may decrease acetaminophen's therapeutic effect; anticholinergic agents (scopolamine) may effect GI absorption; acetaminophen may increase the clearance of lamotrigine; acetaminophen may increase zidovudine concentration and toxicity
FOOD INTERACTIONS — Rate of absorption may be decreased when given with food high in carbohydrates
PREGNANCY RISK FACTOR — B (show table)
REFERENCE RANGE — Acute ingestions: Toxic concentration with probable hepatotoxicity: >200 mcg/mL at 4 hours or 50 mcg/mL at 12 hours after ingestion of overdose
MECHANISM OF ACTION — Inhibits the synthesis of prostaglandins in the CNS and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center
PHARMACOKINETICS Protein binding: 20% to 50%
Metabolism: At normal therapeutic dosages the parent compound is metabolized in the liver to sulfate and glucuronide metabolites, while a small amount is metabolized by microsomal mixed function oxidases to a highly reactive intermediate (N-acetyl-imidoquinone) which is conjugated with glutathione and inactivated; at toxic doses (as little as 4 g in a single day) glutathione can become depleted, and conjugation becomes insufficient to meet the metabolic demand causing an increase in N-acetyl-imidoquinone concentration, which is thought to cause hepatic cell necrosis.
Half-life: Neonates: 2-5 hours Adults: 1-3 hours
Time to peak serum concentration: 10-60 minutes after normal oral doses, but may be delayed in acute overdoses
PATIENT INFORMATION — Avoid alcohol; do not take longer than 10 days without physician's advice
(For additional information see "Acetaminophen: Patient drug information")
ADDITIONAL INFORMATION — Drops may contain saccharin.
Acetaminophen (15 mg/kg/dose given orally every 6 hours for 24 hours) did not relieve the intraoperative or the immediate postoperative pain associated with neonatal circumcision; some benefit was seen 6 hours after circumcision (see Howard, 1994).
There is currently no scientific evidence to support alternating acetaminophen with ibuprofen in the treatment of fever (see Mayoral, 2000).
CANADIAN BRAND NAMES — Abenol®; Apo-Acetaminophen®; Atasol®; Novo-Gesic; Pediatrix; Tempra®; Tylenol®
SYNONYMS — APAP; N-Acetyl-P-Aminophenol; Paracetamol
THERAPEUTIC CATEGORY Analgesic, Non-narcoticAntipyretic
DOSING
(For additional information see "Acetaminophen: Drug information")Neonates: Oral, rectal: 10-15 mg/kg/dose every 6-8 hours as needed International Evidence-Based Group for Neonatal Pain recommendations (Anand, 2001; Anand, 2002): Preterm infants 28-32 weeks: Oral: 10-12 mg/kg/dose every 6-8 hours; maximum daily dose: 40 mg/kg/day Rectal: 20 mg/kg/dose every 12 hours; maximum daily dose: 40 mg/kg/day Preterm infants 32-36 weeks and term infants <10 days: Oral: 10-15 mg/kg/dose every 6 hours; maximum daily dose: 60 mg/kg/day Rectal: Loading dose: 30 mg/kg; then 15 mg/kg/dose every 8 hours; maximum daily dose: 60 mg/kg/day Term infants 10 days: Oral: 10-15 mg/kg/dose every 4-6 hours; maximum daily dose: 90 mg/kg/day Rectal: Loading dose: 30 mg/kg; then 20 mg/kg/dose every 6-8 hours; maximum daily dose: 90 mg/kg/day
Infants and Children: Oral: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses in 24 hours; alternatively, the following doses may be used.
Alternative Acetaminophen Dosing (Oral)1: 6-11 lbs: 0-3 months: 40 mg 12-17 lbs: 4-11 months: 80 mg 18-23 lbs: 1-2 years: 120 mg 24-35 lbs: 2-3 years: 160 mg 36-47 lbs: 4-5 years: 240 mg 48-59 lbs: 6-8 years: 320 mg 60-71 lbs: 9-10 years: 400 mg 72-95 lbs: 11 years: 480 mg 1Manufacturer's recommendations; use of weight to select dose is preferred; if weight is not available, then use age Rectal: 10-20 mg/kg/dose every 4-6 hours as needed. Note: Although the perioperative use of high-dose rectal acetaminophen (eg, 25-45 mg/kg/dose) has been investigated in several studies, its routine use remains controversial; optimal doses and dosing frequency to ensure efficacy and safety have not yet been established; further studies are needed (see Buck, 2001).
Children 12 years and Adults: Oral, rectal: 325-650 mg every 4-6 hours or 1000 mg 3-4 times/day; do not exceed 4 g/day
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet: 500 mg Cetafen Extra® Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Tycolene Maximum Strength, Tylenol® Extra Strength: 500 mg
Caplet, extended release: Tylenol® 8 Hour, Tylenol® Arthritis Pain: 650 mg
Capsule: 500 mg
Elixir: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) Apra Children's: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) [alcohol free; contains benzoic acid; cherry and grape flavors] Mapap Children's: 160 mg/5 mL (120 mL) [alcohol free; contains benzoic acid and sodium benzoate; cherry flavor]
Gelcap: Mapap Extra Strength, Tylenol® Extra Strength: 500 mg
Geltab: Tylenol® Extra Strength: 500 mg
Geltab, extended release: Tylenol® 8 Hour: 650 mg [DSC]
Liquid, oral: 500 mg/15 mL (240 mL) Comtrex® Sore Throat Maximum Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; honey lemon flavor] Genapap™ Children: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry and grape flavors] Silapap®: 160 mg/5 mL (120 mL, 240 mL, 480 mL) [sugar free; contains sodium benzoate; cherry flavor] Tylenol® Extra Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; cherry flavor]
Solution, oral: 160 mg/5 mL (120 mL, 480 mL)
Solution, oral [drops]: 80 mg/0.8 mL (15 mL) [droppers are marked at 0.4 mL (40 mg) and at 0.8 mL (80 mg)] Genapap™ Infant: 80 mg/0.8 mL (15 mL) [fruit flavor] Infantaire: 80 mg/0.8mL (15 mL, 30 mL) Silapap® Infant's: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor]
Suppository, rectal: 120 mg, 325 mg, 650 mg Acephen™: 120 mg, 325 mg, 650 mg FeverALL®: 80 mg, 120 mg, 325 mg, 650 mg Mapap: 125 mg, 650 mg
Suspension, oral: Mapap Children's: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry flavor] Nortemp Children's: 160 mg/5 mL (120 mL) [alcohol free; contains sodium benzoate; cotton candy flavor] Tylenol® Children's: 160 mg/5 mL (120 mL, 240 mL) [contains sodium benzoate; bubble gum yum, cherry blast, dye free cherry, grape splash, and very berry strawberry flavors] Tylenol® Children's with Flavor Creator: 160 mg/5 mL (120 mL) [contains sodium 2 mg/5 mL and sodium benzoate; cherry blast flavor; packaged with apple (4), bubblegum (8), chocolate (4), & strawberry (4) sugar free flavor packets]
Suspension, oral [drops]: Mapap Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor] Tylenol® Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry, dye free cherry, and grape flavors]
Tablet: 325 mg, 500 mg Aspirin Free Anacin® Extra Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Pain Eze, Tylenol® Extra Strength, Valorin Extra: 500 mg Cetafen®, Genapap™, Genebs, Mapap, Tycolene, Tylenol®, Valorin: 325 mg
Tablet, chewable: 80 mg Genapap™ Children: 80 mg [contains phenylalanine 6 mg/tablet; fruit and grape flavors] Mapap Children's: 80 mg [contains phenylalanine 3 mg/tablet; bubble gum, fruit, and grape flavors] Mapap Junior Strength: 160 mg [contains phenylalanine 12 mg/tablet; grape flavor]
Tablet, orally disintegrating: 80 mg, 160 mg Tylenol® Children's Meltaways: 80 mg [bubble gum, grape, and watermelon flavors] Tylenol® Junior Meltaways: 160 mg [bubble gum and grape flavors]
GENERIC AVAILABLE — Yes: Excludes extended release products
ADMINISTRATION — Oral: Administer with food to decrease GI upset; shake suspension well before use; do not crush or chew extended release products
USE — Treatment of mild to moderate pain and fever; does not have antirheumatic or systemic anti-inflammatory effects
ADVERSE REACTIONS Dermatologic: Rash
Hematologic: Blood dyscrasias (neutropenia, pancytopenia, leukopenia)
Hepatic: Hepatic necrosis with overdose
Renal: Renal injury with chronic use
Miscellaneous: Hypersensitivity reactions (rare)
CONTRAINDICATIONS — Hypersensitivity to acetaminophen or any component
PRECAUTIONS — Some products (eg, chewable tablets) contain aspartame which is metabolized to phenylalanine and must be avoided (or used with caution) in patients with phenylketonuria.
G-6-PD deficiency: Although several case reports of acetaminophen-associated hemolytic anemia have been reported in patients with G-6-PD deficiency, a direct cause and effect relationship has not been well established (concurrent illnesses such as fever or infection may precipitate hemolytic anemia in patients with G-6-PD deficiency); therefore, acetaminophen is generally thought to be safe when given in therapeutic doses to patients with G-6-PD deficiency.
WARNINGS — May cause severe hepatic toxicity with overdose. Use with caution in patients with alcoholic liver disease. Chronic daily dosing in adults of 5-8 g of acetaminophen over several weeks or 3-4 g/day for 1 year have resulted in liver damage. Do not exceed maximum daily doses; consider acetaminophen content of combination products when evaluating the dose of acetaminophen.
Some elixir preparations contain benzoic acid; liquid preparations (ie, elixir, liquid, suspension, and drops) may contain sodium benzoate (see Dosage Forms); benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse; avoid use of acetaminophen products containing sodium benzoate in neonates; in vitro and animal studies have shown that benzoate displaces bilirubin from protein binding sites
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP1A2 substrate (minor), CYP2A6, CYP2C9, CYP2D6, CYP2E1 and CYP3A3/4 isoenzyme substrate
Enzyme inducers (barbiturates, carbamazepine, phenytoin, rifampin), carmustine (with high dose acetaminophen), isoniazid, alcohol (especially chronic use) can increase hepatotoxicity; rifampin may decrease acetaminophen's therapeutic effect; anticholinergic agents (scopolamine) may effect GI absorption; acetaminophen may increase the clearance of lamotrigine; acetaminophen may increase zidovudine concentration and toxicity
FOOD INTERACTIONS — Rate of absorption may be decreased when given with food high in carbohydrates
PREGNANCY RISK FACTOR — B (show table)
REFERENCE RANGE — Acute ingestions: Toxic concentration with probable hepatotoxicity: >200 mcg/mL at 4 hours or 50 mcg/mL at 12 hours after ingestion of overdose
MECHANISM OF ACTION — Inhibits the synthesis of prostaglandins in the CNS and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center
PHARMACOKINETICS Protein binding: 20% to 50%
Metabolism: At normal therapeutic dosages the parent compound is metabolized in the liver to sulfate and glucuronide metabolites, while a small amount is metabolized by microsomal mixed function oxidases to a highly reactive intermediate (N-acetyl-imidoquinone) which is conjugated with glutathione and inactivated; at toxic doses (as little as 4 g in a single day) glutathione can become depleted, and conjugation becomes insufficient to meet the metabolic demand causing an increase in N-acetyl-imidoquinone concentration, which is thought to cause hepatic cell necrosis.
Half-life: Neonates: 2-5 hours Adults: 1-3 hours
Time to peak serum concentration: 10-60 minutes after normal oral doses, but may be delayed in acute overdoses
PATIENT INFORMATION — Avoid alcohol; do not take longer than 10 days without physician's advice
(For additional information see "Acetaminophen: Patient drug information")
ADDITIONAL INFORMATION — Drops may contain saccharin.
Acetaminophen (15 mg/kg/dose given orally every 6 hours for 24 hours) did not relieve the intraoperative or the immediate postoperative pain associated with neonatal circumcision; some benefit was seen 6 hours after circumcision (see Howard, 1994).
There is currently no scientific evidence to support alternating acetaminophen with ibuprofen in the treatment of fever (see Mayoral, 2000).
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